Frailty syndrome and associated factors among patients with hypertension: A cross‐sectional study in Kumasi, Ghana

Abstract Background and Aim Frailty is a condition marked by accumulation of biological deficits and dysfunctions that come with aging and it is correlated with high morbidity and mortality in patients with cardiovascular diseases, particularly hypertension. Hypertension continues to be a leading cause of cardiovascular diseases and premature death globally. However, there is dearth of literature in sub‐Saharan Africa on frailty syndrome among hypertensives on medication. This study evaluated frailty syndrome and its associated factors among Ghanaian hypertensives. Methods This cross‐sectional study recruited 303 patients with hypertension from the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Data on sociodemographic, lifestyle and clinical factors were collected using a well‐structured questionnaire. Medication adherence was measured using Adherence in Chronic Disease Scale, and frailty was assessed by Tilburg Frailty Indicator. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism 8.0. p‐value of < 0.05 and 95% confidence interval (CI) were considered statistically significant. Results The prevalence of frailty was 59.7%. The proportion of high, medium and low medication adherence was 23.4%, 64.4% and 12.2%, respectively. Being ≥ 70years (adjusted odds ratio [aOR]: 8.33, 95% CI [3.72–18.67], p < 0.0001), unmarried (aOR: 2.59, 95% CI [1.37–4.89], p = 0.0030), having confirmed hypertension complications (aOR: 3.21, 95% CI [1.36–7.53], p = 0.0080), medium (aOR: 1.99, 95% CI [1.05–3.82], p = 0.0360) and low antihypertensive drug adherence (aOR: 27.69, 95% CI [7.05–108.69], p < 0.0001) were independent predictors of increased odds of developing frailty syndrome. Conclusion Approximately 6 out of 10 Ghanaian adult patients with hypertension experience frailty syndrome. Hypertension complications, older age, being unmarried, and low antihypertensive drug adherence increased the chances of developing frailty syndrome. These should be considered in intervention programmes to prevent frailty among patients with hypertension.

Conclusion: Approximately 6 out of 10 Ghanaian adult patients with hypertension experience frailty syndrome.Hypertension complications, older age, being unmarried, and low antihypertensive drug adherence increased the chances of developing frailty syndrome.These should be considered in intervention programmes to prevent frailty among patients with hypertension.

| INTRODUCTION
Hypertension continues to be a leading cause of cardiovascular disease and premature death globally.It is one of the most common conditions among the general population, contributing negatively to worldwide health and financial issues. 1It is estimated that over 1.28 billion persons worldwide ranges from the ages of 30-79 have hypertension, with approximately 67% residing in low-and middleincome countries. 2In Ghana, hypertension is one of the top reasons of hospitalizations and fatalities.It was Ghana's third most significant cause of hospitalization and death in 2017, accounting for 4.7% of all hospital admissions and 15.3% of all deaths. 3In Ashanti region of Ghana, hypertension affects 37.4% of the population. 4tients' adherence to antihypertensives is crucial to achieve their effects of reduction in stroke incidence, prevention of heart failure exacerbation and low risk of mortality. 5,6About 55% of individuals with hypertension do not follow therapy recommendations, and this has been attributed to low socioeconomic level, comorbidities, age, physical limitations, or frailty syndrome. 7ailty is a syndrome marked by the aggregation of biological deficiencies and dysfunctions resulting from ageing and disrupts the organism's homeostatic balance. 8It is a significant issue, mostly in older adults, with negative consequences for illness outcomes and treatment adherence. 9Frailty raises the likelihood of undesirable health outcomes such as mortality, disability, poor quality of life, hospitalization and institutionalization by making people more vulnerable to stress. 10The prevalence of this condition among community-dwelling older individuals is significant, ranging from 8% to 16%. 11Frailty is associated with higher morbidity and mortality in patients suffering from cardiovascular disease. 12,13It has been proposed that recognizing frailty can aid clinicians in determining procedure risks, evaluating prognosis, and guiding management. 14ailty syndrome in older individuals has received a lot of attention lately.It is estimated 15%-20% of people over 60% and 30% of patients over 80 are affected by frailty syndrome. 15With the life expectancy of Ghanaians at 64 years, 16 the prevalence of frailty may be higher at even younger ages in the general Ghanaian population.It is advised that, better knowledge of frailty in cardiac care, especially in older adults should be enhanced. 17In all, 25%-50% of patients with a cardiac disease suffer from frailty syndrome. 15me of these include patients with hypertension.Despite the increasing prevalence of frailty, its associated factors, including medication adherence among patients with hypertension have not been explored in sub-Saharan Africa.For the first time, we determined the prevalence and predictors of frailty syndrome in a sample of Ghanaian patients with hypertension.

| Study design
This study was a cross-sectional study design.The study sought to determine the prevalence and factors associated with frailty syndrome among patients with hypertension from Janury 2022 to September 2022.

| Study site
The study was conducted at the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST) in Kumasi, Ghana.Kumasi is the regional capital of the Ashanti Region of Ghana, with an estimated population of 200,000 (Figure 1).The hospital offers services in general medical care as well as specialist services.
The geographical location of the 135-bed hospital, and the road network of Kumasi make the hospital accessible.As such, referrals are received from other centers, making our study population quite representative.

| Study population
The study population included adult patients (40 years and above) with clinically diagnosed hypertension in the outpatient department (OPD) at the University Hospital, KNUST, Kumasi.

| Sample size
The sample size was estimated using the Cochran formula; The minimum number of participants required was 213.
However, we enrolled 303 participants into the study to increase the statistical power.

| Inclusion and exclusion criteria
The study enrolled clinically diangosed hypertensives aged 40 years and above, who were on at least one antihypertension medication.Patients below the age of 40 years, patients with no history of hypertension, and patients who had not been treated with any antihypertensive drug or with cognitive impairments were excluded from the study.

| Data collection
We used a well-structured questionnaire to collect sociodemographic, lifestyle, and clinical data from participants.In addition, standardized instruments, which included Adherence in Chronic Disease Scale (ACDS) 19 and Tilburg Frailty indicator (TFI), were used to measure adherence and frailty, respectively, among study participants.Before the commencement of the study, these questionnaires were piloted among hypertensives at Kumasi South Government Hospital, Kumasi, and reliability was determined using Cronbach's α.
F I G U R E 1 Map of University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.

| Measurement of medication adherence using ACDS
To assess study participants' compliance with medication adherence, we employed the ACDS.The underlying assumption of ACDS is that in pharmacology, only great adherence is indicative of an effective therapeutic plan.There were seven questions on the scale, and each had five options.Questions 1-5 dealt with behaviors that directly influence adherence, whereas questions 6-7 dealt with circumstances and viewpoints that do the same.The ACDS score ranges from 0 to 28 points.Higher results mean higher adherence.Thus, above 26 points indicated good adherence, between 21 and 26 points indicated medium adherence, and below 21 points indicated low adherence. 199 | Measurement of frailty syndrome using the TFI The TFI was created by Gobbens et al. 20  Frailty is diagnosed at a total TFI score ≥ 5. 20 The TFI has been proven to be reliable and valid for assessing frailty.

| Instrument validity and reliability
The questionnaire was designed based on validated questions from previous studies.Before the study commenced, the questionnaire was pre-tested in different hypertensive populations at the Suntreso Hospital in Kumasi, and all misleading and ambiguous questions were corrected.Moreover, the internal consistency for the reliability of the ACDS and TFI questionnaire was computed using Cronbach's α.

| Prevalence of antihypertensive drug adherence and frailty among study participants
The majority (64.4%) of the study participants had medium adherence to their antihypertensive drugs, followed by high adherence (23.4%), and 12.2% had low adherence (Figure 2A).On the other hand, more than half (59.7%) of the participants had frailty syndrome (Figure 2B).

| Clinical and lifestyle predictors of frailty syndrome
In a univariate logistic regression model, taking any medication apart from the antihypertensives (cOR: 3. p < 0.0001) independently increased odds of developing frailty syndrome compared to high adherence (Figure 3B).

| DISCUSSION
Hypertension continues to be a leading cause of cardiovascular disease and premature death globally.Despite the increasing prevalence of frailty, its associated factors, including medication adherence among patients with hypertension, have not been explored in Sub-Saharan Africa.In this study, the prevalence of frailty among the study participants was 59.7%.Previous studies have reported frailty prevalence among community dwelling older adults in Ghana as 37.9%. 21Our finding is much higher than the proportion of frailty found by Aprahamain et al. 22 (14.8%).In their study, though conducted in an outpatient center like ours, the inclusion criterion was open to all older adults presenting to the center and not focused on individuals having hypertension as a baseline.The significant difference, therefore, may likely be due to the underlying hypertension in all our participants and the high prevalence of combined hypertension and diabetes mellitus.Likewise, Ma et al. 23 reported a frailty proportion of 13.8% among older adults in China, which is much lower compared to what was obtained in this current study.Again, their study looked at community-dwelling older adults with individuals diagnosed with hypertension and those undiagnosed, but had measured systolic blood pressures of over 140 and diastolic blood pressures over 90 during the study.We believe these differences are partly related to the varying socio-genetic factors but, more importantly, the fact that we focused on a population who were all hypertensives seeking medical care for that with over 50% having concomitant diabetes mellitus.
We found being 70 years and above, being unmarried, having confirmed hypertension complications and medium and low antihypertensive drug adherence were independently associated with increased odds of developing frailty syndrome.Female participants were more likely to be frail than their male counterparts and age was also found to be an independent predictor of frailty syndrome.These findings are consistent with results from Gobbens and Assen, 24 who reported age as a determinant of frailty and reported females to be more affected than males.In another study, Fattori et al., 25 who examined a group of Brazilian patients, also found that the prevalence of frailty syndrome was higher in females than in males.
The present study further confirms increasing age, female sex, and presence of chronic medical diseases, especially in older adults, as independent risk factors of frailty.Furthermore, it reinforces the significant impact of the latter. (A)

(B)
F I G U R E 2 Prevalence of antihypertensive drug adherence (A) and frailty (B) among study participants.
Despite the findings above, women have documented higher life expectancies than men in most countries. 26,27This inconsistency in the likelihood of frailty and mortality in females is likely due to the effect of riskier lifestyles in men, such as smoking, alcohol use, that are associated with higher cardiovascular risk. 28Moreira and Lourenco. 29reported marital status was associated with the development of frailty.In their study, individuals who were unmarried were at increased risk of developing frailty syndrome.
This is consistent with our study in which being unmarried was an independent predictor of frailty syndrome.The positive association could be attributed to the psychological, emotional and physical support provided by married couples that has been found to limit depression and the likelihood of frailty.Similarly, a study by Monin et al. 30 revealed that, an individual's frailty is predicted by the spouse's or partner's relationship effects.Furthermore, our study found the presence of hypertension complications as an independent predictor of frailty syndrome.In this study, the proportion of high adherence among hypertension patients was 23.4%.This was lower compared to similar local studies, one at Korle-Bu Teaching Hospital, Ghana (47.7%), 31 and a multicenter study in Ghana and Nigeria (33.3%).On the other hand, Sarkodie et al. 32 reported a much lower adherence to antihypertensive medication (7.0%), at the Komfo Anokye Teaching Hospital, Ghana.These differences in medication adherence may be due to variations in the methodologies used in measuring medication adherence aside the socioeconomic factors and beliefs identified in these studies.This study revealed low medication adherence as an independent predictor of frailty syndrome.The finding is in line with a study by Jankowska

| CONCLUSION
We found frailty to be present in approximately 6 out of 10 Ghanaian adult patients with hypertension, and that the presence of hypertension complications, advancing age, not being married, and low antihypertensive drug adherence increase the chances of developing frailty syndrome.Therefore, we recommend interventions aimed at preventing frailty among patients with hypertension to include measures that limit these factors.
Z is the standard normal variate at a confidence interval (CI) of 95% = 1.96, p is the estimated prevalence of hypertension (16.6%) in Ashanti region,18 e is the margin of error (0.05).n (Minimum number of participants) TFI is divided into two components.The participant's sociodemographic data are covered in part one, and 15 self-reported questions are separated into three categories: social, psychological, and physical.Eight questions in the physical domain are scored from 0 to 8 points and pertain to physical health, unexplained weight loss, difficulties walking, balance, hearing and vision issues, hand strength, and physical exhaustion.The psychological domain consists of four items (0-4 points each) that address cognition, depressive symptoms, anxiety, and coping.The social domain consists of three questions (0-3 points) about interacting with others, receiving social support, and living alone.Eleven of the TFI's second part's questions have only two possible answers: yes or no, whereas the other questions have three (yes, no, and occasionally)."Yes" or "Sometimes" responses receive one point apiece, while "no" responses receive zero points.The total score might be between 0 and 15: The fragility syndrome increases with score.
et al.,7 who found that adherence was lower in people with frailty syndrome.This is the first study to report frailty syndrome among patients with hypertension in Ghana, Although the prevalence of frailty was high because of the study settings and population, the determinants are consistent with that of studies from other populations.The findings may be limited.Our analysis did not include other chronic conditions besides hypertension and diabetes.Secondly, this study did not include drug interactions and adverse effects in the case of individuals on other medications aside from antihypertensive medication.We therefore recommend that future studies should include these factors to assess more potential risk factors of frailty syndrome among patients with hypertension.

Ethical approval was sought from the Committee on Human Research, Publication and Ethics, School of Medicine and Dentistry,
Categorical variables were presented as frequencies and percentages.Univariate and multivariate logistic regression prediction models were employed to predict the association between study variables and frailty syndrome using frailty syndrome as the dependent variable.A p-value of < 0.05 and a 95% CI were considered statistically significant.Clinical and lifestyle characteristics of study participantsThe majority (61.1%) of the study participants were taking other medications besides the antihypertensives.Over two-thirds (78.2%) of the study participants had no confirmed hypertension complications.
Data obtained from participants were coded into Microsoft Excel 2019 and analyzed using Statistical Package for Social Sciences (SPSS) Version 26.0 and GraphPad prism version 8.0 (GraphPad software; www.graphpad.com).
Clinical and lifestyle characteristics of study participants.